Techniques of tissue engineering employing biocompatible scaffolds provide viable alternatives to materials currently used in prosthetic and reconstructive surgery. These materials also hold promise in the formation of tissue or organ equivalents to replace diseased, defective, or injured tissues. In addition, biocompatible scaffolds can be used to form biodegradable materials which may be used for controlled release of therapeutic materials (e.g. genetic material, cells, hormones, drugs, or pro-drugs) into a predetermined area. However, most polymers used today to create these scaffolds, such as polylactic acid, polyorthoesters, and polyanhydrides, are difficult to control and result in, among other things, poor cell attachment and poor integration into the site where the tissue engineered material is utilized. Accordingly, focus has shifted to scaffolds formed from synthetic biomolecules, more particularly biomimetic scaffolds capable of in situ self-assembly.
The preparation of any synthetic material with structure on the nanoscale that mimics natural tissue is a challenging problem. One approach has been to prepare molecules that spontaneously assemble into fibrils similar in morphology to the proteins and proteoglycans that compose the natural extracellular matrix. In contrast to most synthetic biopolymers, the use of small, self-assembling molecules facilitates control of chemical and structural properties of these macromolecular assemblies. 1-12 To that end, peptide amphiphiles have recently been shown to self-assemble under suitable conditions to form fibril-like micelles (referred to in the art as “nanofibers”), such nanofibers having particular utility as biocompatible scaffolds, more particularly in the area of tissue engineering. 13-26 However, many such molecules have proven difficult to synthesize and/or purify on a large scale. This is due in part to the molecules' zwitterionic nature (i.e., carrying both positive and negative charges), and their propensity to aggregate in solution due to the relative large proportion of non-polar amino acid residues. 1, 27, 28 The present invention addresses this need by providing novel peptide amphiphile molecules and compositions having improved physical and chemical properties that enable automated synthesis and purification to the level required for in vivo applications. In addition, gels of the improved peptide amphiphile compositions of the present invention formed in artificial cerebrospinal fluid (CSF) 29-31 are demonstrated herein to possess an increased mechanical stiffness which better mimics the mechanical properties of natural central nervous system tissues, which, in turn, should correlate to improved neurogenic differentiation of mesenchymal stem cells. 32 